本文選題：高致病性豬繁殖與呼吸綜合征病毒 + 糖皮質(zhì)激素��； 參考：《中國農(nóng)業(yè)科學(xué)院》2015年碩士論文

【摘要】：豬繁殖與呼吸綜合征(Porcine Reproductive and Respiratory Syndrome,PRRS)是PRRS病毒(PRRSV)引起的一種急性傳染性動(dòng)物疫病。自2006年以來,高致病性PRRS(HP-PRRS)在我國暴發(fā)并廣泛流行,給我國養(yǎng)豬業(yè)帶來嚴(yán)重的經(jīng)濟(jì)損失。目前認(rèn)為該病毒對(duì)感染動(dòng)物機(jī)體各組織器官具有廣泛的致病性,并能夠引起免疫抑制,是引起豬免疫功能紊亂的重要病原之一。哺乳動(dòng)物下丘腦-垂體-腎上腺(Hypothalamus-Pitutary-Adrenal,HPA)系統(tǒng),在病原微生物感染或應(yīng)激條件下,會(huì)被高水平的促炎性細(xì)胞因子(Proinflammatory Cytokines)激活,激活后通過釋放以糖皮質(zhì)激素(Glucorcoticoids,GCs)為主的一系列內(nèi)分泌激素來參與調(diào)節(jié)機(jī)體免疫功能,是機(jī)體神經(jīng)-內(nèi)分泌-免疫環(huán)路調(diào)控的中樞環(huán)節(jié),在維持內(nèi)環(huán)境穩(wěn)態(tài)中發(fā)揮重要作用。本實(shí)驗(yàn)室前期研究表明,HP-PRRSV感染仔豬早期能夠在外周血中檢測到大量的促炎性細(xì)胞因子,病豬表現(xiàn)典型的高熱癥狀,并伴隨嚴(yán)重的胸腺萎縮和胸腺細(xì)胞凋亡,死亡率顯著高于經(jīng)典毒株感染。本研究以HP-PRRSV HuN4毒株接種斷奶仔豬,觀察攻毒后不同時(shí)間仔豬HPA軸器官及其釋放激素的變化,并通過增強(qiáng)和抑制HPA軸的功能,從免疫系統(tǒng)與神經(jīng)內(nèi)分泌系統(tǒng)相互作用的水平上研究PRRSV在豬體內(nèi)的致病機(jī)理。研究結(jié)果表明:HP-PRRSV感染后7-10 d,仔豬外周血CRH、ACTH和GCs3種激素的水平發(fā)生顯著變化,外周血中促炎性因子IL-1β,IL-6,TNF-α的轉(zhuǎn)錄水平顯著升高;病理組織學(xué)觀察顯示,病毒感染后7-10 d,仔豬下丘腦血管周圍炎性細(xì)胞浸潤,小膠質(zhì)細(xì)胞結(jié)節(jié)并伴隨細(xì)胞凋亡。使用糖皮質(zhì)激素受體特異性抑制劑米非司酮(RU486)處理仔豬并接種HP-PRRSV,實(shí)驗(yàn)組同直接攻毒對(duì)照組相比,仔豬死亡率明顯升高,攻毒后10 d肺部有明顯的化膿性肺炎的病理變化。進(jìn)一步對(duì)感染仔豬使用糖皮質(zhì)激素類似物地塞米松,發(fā)現(xiàn)雖然感染仔豬外周血內(nèi)促炎性細(xì)胞因子水平降低,外周血淋巴細(xì)胞亞群也趨于正常,但高熱癥狀無法緩解,死亡率和肺臟及胸腺病理變化較單獨(dú)攻毒組更加嚴(yán)重。以上實(shí)驗(yàn)結(jié)果表明HP-PRRSV感染誘導(dǎo)仔豬HPA軸系統(tǒng)的變化對(duì)機(jī)體起到了一定的正向作用,單獨(dú)使用糖皮質(zhì)激素受體特異性抑制劑RU486及糖皮質(zhì)激素類似物地塞米松均打破了病毒感染與HPA軸反應(yīng)的平衡,增強(qiáng)了HP-PRRSV感染仔豬造成的損傷。該結(jié)果對(duì)獸醫(yī)臨床用藥的選擇及畜牧飼料添加劑的選擇具有重要的指導(dǎo)意義,為進(jìn)一步研究HP-PRRSV致病機(jī)制的提供了新的實(shí)驗(yàn)依據(jù)。
[Abstract]:Porcine Reproductive and Respiratory Syndromeg PRRSs (PRRSs) is an acute infectious animal disease caused by PRRS virus. Since 2006, HP-PRRSs (highly pathogenic PRRSs) have been outbreak and widespread in China, which has brought serious economic losses to the pig industry in China. At present, it is considered that the virus has extensive pathogenicity to various tissues and organs of infected animals, and can cause immunosuppression, and it is one of the important pathogens of swine immune dysfunction. The Hypothalamus-Pitutary-Adrenalant (HPA) system of mammalian hypothalamus-pituitary-adrenal gland (Hypothalamus-Pitutary-Adrenalalus) is activated by a high level of proinflammatory cytokines (Proinflammatory Cytokines) under infection or stress by pathogenic microorganisms. After activation, a series of endocrine hormones, mainly glucocorticoid (GCs), are released to regulate the immune function of the body, which play an important role in maintaining the homeostasis of the internal environment. Previous studies in our laboratory showed that a large number of pro-inflammatory cytokines could be detected in peripheral blood of piglets infected with HP-PRRSv in early stage. The pigs showed typical hyperpyretic symptoms, accompanied by severe thymus atrophy and thymocyte apoptosis. The mortality rate was significantly higher than that of classical strain infection. In this study, weaning piglets were inoculated with HP-PRRSV HuN4 strain to observe the changes of HPA axis organs and their releasing hormones at different time after inoculation, and to enhance and inhibit the function of HPA axis. The pathogenesis of PRRSV in pigs was studied from the level of interaction between immune system and neuroendocrine system. The results showed that the levels of CRHP-PRRSv ACTH and GCs3 in peripheral blood of piglets changed significantly at 7-10 days after infection, and the transcription level of IL-1 尾 -IL-6 TNF- 偽 in peripheral blood increased significantly. From 7 to 10 days after virus infection, inflammatory cells infiltration and microglial nodule accompanied by apoptosis were observed in hypothalamic perivascular inflammatory cells of piglets. The piglets were treated with glucocorticoid receptor specific inhibitor Mifepristone RU486) and inoculated with HP-PRRSV.The mortality of the piglets in the experimental group was significantly higher than that in the control group, and there were obvious pathological changes in the lungs of suppurative pneumonia 10 days after the attack. Further more, dexamethasone, a glucocorticoid analogue, was used in infected piglets. It was found that although the levels of proinflammatory cytokines in peripheral blood of infected piglets decreased and the lymphocyte subsets of peripheral blood tended to be normal, the symptoms of hyperthermia could not be alleviated. The mortality and pathological changes of lung and thymus were more serious than those of control group. The results showed that the changes of HPA axis system induced by HP-PRRSV infection had a positive effect on the body. RU486, a glucocorticoid receptor specific inhibitor, and dexamethasone, a glucocorticoid analogue, broke the balance between viral infection and HPA axis reaction, and enhanced the damage caused by HP-PRRSV infection in piglets. The results are of great significance for the selection of veterinary drugs and animal feed additives, and provide a new experimental basis for the further study of the pathogenesis of HP-PRRSV.
【學(xué)位授予單位】：中國農(nóng)業(yè)科學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：S858.28

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本文編號(hào)：1983046